DNA Aptamers Offer New Tool for Easy Alzheimer's Blood Test

Alzheimer’s disease is the most common cause of dementia and is marked by progressive loss of nerve cells that begins many years before symptoms become noticeable. Detecting early signs of neurodegeneration is critical for improving diagnosis and monitoring disease progression. Neurofilament light chain (NfL), a structural protein released into cerebrospinal fluid and blood when neurons are damaged, has emerged as an important biomarker for neurodegeneration and is increasingly used to monitor diseases such as Alzheimer’s disease. However, current blood tests rely on antibody-based immunoassays that can be expensive and difficult to standardize. Researchers have now developed a new molecular tool that may enable more accessible blood-based detection of NfL.

Scientists from the Tokyo University of Science (Tokyo, Japan) in collaboration with Tokyo University of Agriculture and Technology (Tokyo, Japan), have developed the first DNA aptamers capable of binding NfL. The team developed synthetic DNA aptamers—short, single-stranded DNA molecules designed to bind specific proteins with high affinity and specificity. The team generated the aptamers using the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method, screening large libraries of DNA sequences through multiple selection cycles.

After seven rounds of screening, the researchers identified 86 candidate aptamers, which were refined to 30 promising sequences capable of recognizing the full-length NfL protein. Two aptamers, MN711 and MN734, demonstrated particularly strong binding to NfL with dissociation constants of 11 nM and 8.1 nM, levels comparable to commercially available antibodies used in current diagnostic tests. The aptamers showed high specificity, binding only to NfL while avoiding other Alzheimer’s-related biomarkers such as amyloid beta and phosphorylated tau.

They were also found to recognize a specific region of the NfL protein corresponding to amino acid residues 281–338, which are present in NfL fragments circulating in human blood plasma. Importantly, the findings, published in Biochemical and Biophysical Research Communications, show that the aptamers maintained their binding capability when tested in human plasma samples, suggesting potential for use in blood-based diagnostic systems.

Unlike antibodies, DNA aptamers can be chemically synthesized with minimal batch variation and can be easily modified to attach to sensor surfaces. These properties make them well-suited for integration into electrochemical biosensors and portable diagnostic devices. The researchers believe these aptamers could support the development of cost-effective point-of-care diagnostic tools for monitoring neurodegeneration and tracking disease progression in Alzheimer’s disease and other neurological disorders.

"We have reported the world's first DNA aptamer that binds to NfL, which is released into the blood in response to neurodegeneration in various neurodegenerative diseases,” said Associate Professor Kaori Tsukakoshi, who led the study. “The developed aptamer has a binding affinity comparable to commercially available antibodies, and is expected to have a variety of applications in the future, such as diagnosing the progression of AD."

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Tokyo University of Science
Tokyo University of Agriculture and Technology